This prospective study investigated the relationship between levels of anxiety and depression before the start of chemotherapy and the development and level of CIPN during and after treatment. Our results indicate that pre-treatment anxiety but not depressive symptoms, may be a risk factor for developing CIPN in women with breast cancer during and after treatment with taxane-based (neo)adjuvant chemotherapy. These results are in line with Lee’s study that also found an association between pre-treatment anxiety and CIPN . The present study adds to this finding by showing that more anxious patients experience more neuropathy before start and during chemotherapy and that, 6 months after ending chemotherapy, neuropathic symptoms increase even further. In contrast, less anxious patients start at a lower level of neuropathy and although showing an increase in neuropathic symptoms during chemotherapy this level is much lower than in the more anxious group and does not increase after ending chemotherapy.
Both psychological and biological effects of anxiety need to be considered when explaining the association between anxiety and the development of CIPN. Studies have shown that people with high levels of anxiety may be hypersusceptible to pain [19, 20], partly because they are more inclined to catastrophic thinking. [21, 22]. Catastrophic thinking is characterized by attention to threat, overemphasis of the probability of a catastrophic outcome, and rumination about the worst possible consequences. It seems to play a unique role in the experience of higher levels of physical disability and negative physical sensations, like pain [23, 24], because it focuses the attention on the pain. This focus on pain may even be exacerbated when being informed by the medical specialist about the possible side effects of chemotherapy such as neuropathic symptoms. More anxious patients might be more suggestible to the negative expectations about getting pain (nocebo-effect) which may function as a self-fulfilling prophesy [25, 26]. In addition to psychological mechanisms, biological factors may explain the relationship between anxiety and the development of more CIPN. More anxious patients may exhibit higher levels of proinflammatory cytokines interleukin-6 (IL-6) [27–29], which might interfere with recovery from the nerve injury in CIPN, resulting in more CIPN over time [30, 31]. Interestingly, in this study as well as in the study by Lee (2018) no relationship between depressive symptoms and the development of neuropathy was found. More research into the underlying mechanisms is needed to examine why pretreatment depression is not associated with CIPN severity and development while it has been related to more physical pain in other populations .
Neuropathy is a common adverse effect of taxane based chemotherapy, but also of other anticancer drugs and may last for months and even years . Given the increasing number of cancer survivors, there is a urgent need for prevention and treatment strategies for patients with CIPN. The burden experienced by neuropathy may impact optimal cancer treatment by limiting the dose of the anticancer drugs or discontinuing the treatment  and may worsen global quality of life and physical, role, cognitive, and social functioning compared to survivors without CIPN [34, 35]. To date, no treatment can be proposed as a gold standard to prevent or treat CIPN [7, 33, 36]. The results of this study might open the door for studies investigating interventions that may help prevent the development of excessive neuropathy by reducing pre-treatment anxiety. Till date, most psychological interventions focus on reducing or dealing with neuropathy after it developed [34, 37]. Whether psychological and/or pharmacological interventions with the aim of reducing anxiety before chemotherapy may have a positive impact on the development of CIPN should be investigated in future studies.
This study has several strengths such as the use of validated measures for CIPN, anxiety and depression. For the degree of CIPN we have used the EORTC-QLQ-CIPN20. This measure has a strong association with the often used NCI-CTCAE . While both measures are validated, the QLQ-CIPN20 questionnaire provides more detailed information, distinguishes more subtle degrees of neuropathy, and is more responsive to change over time . To detect subtle changes in level of neuropathy is especially important in the case of prevention. Moreover, CIPN was assessed four times in a 9-month period. Data was analyzed using mixed model analyses which is an extension of a linear regression model with the advantage that it focuses on individual patient’s patterns of scores through time rather than on mean values at each of the time points. A mixed model acknowledges that differences at later time points may be due to baseline effects, and that the four separate scores over time by the same subject are correlated. A limitation of the present study is the relatively small sample size and short follow-up period. CIPN may develop months to years after ending chemotherapy [4, 15, 39]. Long term research is required to investigate whether the effect of pre-treatment anxiety on the development of CIPN remains.
In conclusion, the level and persistence of CIPN after taxane based chemotherapy seems to be associated with preexisting anxiety. Consequently, future studies may investigate the mechanisms by which anxiety influences CIPN and whether interventions targeting pre-treatment anxiety could lessen the development of CIPN.